A randomized controlled, open‐label early phase II trial comparing incidence of FOLFIRI.3‐induced diarrhoea between Hangeshashinto and oral alkalization in Japanese patients with colorectal cancer

Abstract

What is known and objective: We conducted a pilot clinical trial to investigate whether Hangeshashinto (TJ-14) could be substituted for oral alkalization in patients scheduled to undergo chemotherapy by FOLFIRI.3 regimen for colorectal cancer (CRC). Methods:Patients with CRC were randomized 1:1 to a TJ-14 (7.5 g/day) group or an oral alkalization (sodium bicarbonate, 1.8 g/day; ursodeoxycholic acid, 300 mg/day) group. The primary endpoint was incident of late-onset diarrhoea. A total of 30 patients were randomized to either the TJ-14 group or the alkalization group. Results and discussion:There was no statistical difference in age, concomitantly used drugs or UGT1A1 genotypes between the groups. In the alkalization group (n = 15), the frequency of grade 0/1/2 and grade 3 diarrhoea was 73% and 27%, respectively. In the TJ-14 group (n = 14), the frequency of grade 0/1/2 and grade 3 diarrhoea was 79% and 21%, respectively. Grade 4 diarrhoea was not observed in either group. There was no statistically significant difference in other adverse events or in response to FOLFIRI.3 between the groups. What is new and conclusion:This pilot trial suggests that TJ-14 is a promising alternative treatment option to reduce FOLFIRI.3-induced late-onset diarrhoea, although additional clinical study with a larger number of patients is necessary to confirm these results. K E Y W O R D S alkalization, diarrhoea, FOLFIRI.3, Hangeshashinto, RCT

How to Balance Prognostic Factors in Controlled Phase II Trials: Stratified Permuted Block Randomization or Minimization? An Analysis of Clinical Trials in Digestive Oncology

“…The PRISMA flow diagram of the selected articles is presented in Figure 2 . After reconciliation, 40 articles were included in the analyses [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ] ( File S1 Table S1 ). Of these 40 articles, 14 had a last-author affiliation from Asia (35%), 16 from Europe (40%), and 10 from North America (25%).…”

Efficacy of Hangeshashinto in the Prevention of Chemotherapy-Induced Diarrhea: A Systematic Review and Meta-Analysis

“…The remaining 26 reports were screened by full-text review. Finally, three studies were selected for meta-analysis [ 16 , 17 , 22 ].…”

“…In addition, Hangeshashinto is less expensive and could be a potential alternative to existing therapeutic agents for chemotherapy-induced diarrhea [ 14 - 16 ]. However, studies on the efficacy of Hangeshashinto in preventing chemotherapy-induced diarrhea have reported conflicting results [ 17 ]. Evaluating the effects of Hangeshashinto may reduce the use of and adverse events caused by drug therapy for chemotherapy-induced diarrhea.…”

Clinical review of alkalization therapy in cancer treatment

“…It was reported that intestinal alkalization by bicarbonate treatment showed a preventive effect for irinotecan-induced diarrhea in both in vivo and in vitro studies (57). In clinical studies investigating whether oral administration of bicarbonate (1.8-2.0 g/day) has preventive effects for irinotecan-induced diarrhea in patients with non-small cell lung cancer, small cell lung cancer, and colorectal cancer, no significant differences were observed in the effects of chemotherapy between the bicarbonate-treated and non-treated groups (58,59). However, the effects of bicarbonate administration as alkalization therapy requires further investigation, as the number of patients these previous were also small, the amount of bicarbonate consumption was low, and urine pH was not measured.…”